Dendrodedritic synapses in the olfactory bulb play a crucial role in processing and modulating olfactory sensory information. GABA is hypothesized to be an inhibitory neurotransmitter at the dendrodendritic synapses, based primarily on electrophysiological evidence. This proposal is designed to determine the ability of GABA to meet the neurochemical criteria for neurotransmitter at the dendrodendritic synapses in the olfactory bulb. The subcellular distribution of the specific Na+-independent GABA binding and the neuronal Na+-dependent high-affinity uptake system specific for GABA will be determined and kinetically characterized. The neurophamacological specificity of GABA binding and uptake will be assessed using known agonists, antagonists and inhibitors. It is hypothesized that the Na+-dependent high-affinity GABA uptake system will be neuropharmacologically specific and will be primarily associated with the synaptosomal fraction derived from the dendrodendritic synapses. The investigator has already isolated dendrodendritic synaptosomes from rat olfactory bulbs and has demonstrated the presence of substantial quantities of glutamic acid decarboxylase, the rate-limiting enzyme that catalyses the synthesis of GABA. Preliminary results indicate that the binding of GABA to membranes prepared from a crude dendrodendritic synaptosomal fraction appears to be Na+-independent, reversible and saturable. A large proportion (30%) of CNS synapses are GABAergic and abberations in the GABA system have been implicated in neurological disorders (epilepsy, Huntington's chorea). Sine the olfactory bulb is such a rich source of GABAergic neurons, it has the potential of serving as a model for the GABA system in general.